JPH0437542B2 - - Google Patents
Info
- Publication number
- JPH0437542B2 JPH0437542B2 JP60104883A JP10488385A JPH0437542B2 JP H0437542 B2 JPH0437542 B2 JP H0437542B2 JP 60104883 A JP60104883 A JP 60104883A JP 10488385 A JP10488385 A JP 10488385A JP H0437542 B2 JPH0437542 B2 JP H0437542B2
- Authority
- JP
- Japan
- Prior art keywords
- sample
- matrix agent
- shaft
- ionization
- introduction chamber
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000002500 ions Chemical group 0.000 claims description 39
- 239000002245 particle Substances 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- 239000011159 matrix material Substances 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 13
- 239000011164 primary particle Substances 0.000 claims description 12
- 238000004949 mass spectrometry Methods 0.000 claims description 11
- 238000006073 displacement reaction Methods 0.000 claims description 9
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- 239000003463 adsorbent Substances 0.000 claims description 6
- 238000004458 analytical method Methods 0.000 claims description 6
- 238000004587 chromatography analysis Methods 0.000 claims description 5
- 150000002894 organic compounds Chemical class 0.000 claims description 5
- 239000012212 insulator Substances 0.000 claims description 4
- 238000011161 development Methods 0.000 claims description 3
- 235000011187 glycerol Nutrition 0.000 claims description 3
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 claims description 3
- 238000005259 measurement Methods 0.000 description 14
- 238000001004 secondary ion mass spectrometry Methods 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 8
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 238000010586 diagram Methods 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 150000001793 charged compounds Chemical class 0.000 description 4
- 238000004891 communication Methods 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical group [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000010265 fast atom bombardment Methods 0.000 description 3
- 238000010884 ion-beam technique Methods 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000002359 drug metabolite Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical class CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Analysing Materials By The Use Of Radiation (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Electron Tubes For Measurement (AREA)
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、試料走査形質量分析に関し、とりわ
け、二次イオン質量分析（SIMS）および高速原
子衝突法（FAB）における改良に係る。DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to sample scanning mass spectrometry, and in particular to improvements in secondary ion mass spectrometry (SIMS) and fast atom bombardment (FAB).
分離機能と測定機能を併有する既製の質量分析
法には、質量分析にガスクロマトグラフを組み合
わせたGC／MSおよび同じく液体クロマトグラ
フを組み合わせたLC／MSがある。これらは、何
れも複雑で高価な装置を使用する必要があるばか
りでなく対象とする試料によつては適用が全く不
可能なことがある。
Off-the-shelf mass spectrometry methods that have both separation and measurement functions include GC/MS, which combines mass spectrometry with gas chromatography, and LC/MS, which also combines mass spectrometry with liquid chromatography. All of these methods not only require the use of complicated and expensive equipment, but also may be completely impossible to apply depending on the target sample.
ある種の医薬、医薬の代謝物、生体内物質ある
いは糖類、およびペプチドなどの混合物は、GC
あるいはLCによる分離段階で分解することがあ
る。また、分離手段を連結した質量分析に際して
も、分子がイオン化する前段階の蒸発・昇華にお
いて分解が起こり測定できない場合がある。
Mixtures such as certain drugs, drug metabolites, biological substances or sugars, and peptides are subject to GC.
Alternatively, it may be decomposed during the LC separation step. Furthermore, even in mass spectrometry coupled with separation means, decomposition may occur during evaporation and sublimation before molecules are ionized, making measurement impossible.
本発明は、こうした種々の問題点を解決し、こ
れまで分離・測定が困難であつた不安定な混合物
を容易に各成分ごとに測定出来る改良された試料
走査形の質量分析方法と当該試料の走査装置を提
供することをその目的とする。
The present invention solves these various problems and provides an improved sample scanning mass spectrometry method that can easily measure each component of unstable mixtures that have been difficult to separate and measure. Its purpose is to provide a scanning device.
すなわち本発明によれば、質量分析計の試料イ
オン化室内において直線変位可能に配置された導
電性クロマトグラフ・シート表面の吸着剤薄層に
各成分を表わすスポツトの列としてクロマトグラ
フ展開された混合物試料に対し、その各スポツト
に順次衝突する一次粒子の連続的な流れを形成す
ること、および該一次粒子との衝突によつて発生
した該試料の各成分を表わす二次イオン粒子を順
次、質量分析計の分析部に送り込むことを特徴と
する試料走査形質量分析方法が提供される。 That is, according to the present invention, a mixture sample is chromatographically developed as a row of spots representing each component on a thin layer of adsorbent on the surface of a conductive chromatograph sheet arranged to be linearly displaceable in the sample ionization chamber of a mass spectrometer. Then, a continuous flow of primary particles is formed that collides with each spot in sequence, and secondary ion particles representing each component of the sample generated by the collision with the primary particles are sequentially subjected to mass spectrometry analysis. A sample scanning mass spectrometry method is provided, which is characterized in that the sample is sent to an analysis section of a analyzer.
ここで「導電性クロマトグラフ・シート」と
は、基板がたとえばアルミ箔などの市販の導電性
クロマトグラフ・シート〔たとえば、メルク社
（MerckAG）より得られるTLCアルミシートシ
リカゲル60Art.5583〕はもちろん、吸着剤を絶縁
性基板上に展着したシートであつても、導電性の
溶媒などに浸漬して一時的に導電性としたものを
も含むものとする。 Here, "conductive chromatography sheet" refers to commercially available conductive chromatography sheets whose substrate is aluminum foil (for example, TLC aluminum sheet silica gel 60Art.5583 obtained from Merck AG), The term also includes a sheet in which an adsorbent is spread on an insulating substrate, which is made temporarily conductive by immersing it in a conductive solvent or the like.
ここで「一次粒子」とは、SIMSの場合におけ
る稀ガスなどの一次イオン粒子ばかりでなく、
FABの場合の非荷電粒子（加速されたのち荷電
を除去されたもの）をも含む。また「試料イオン
化室」は、通常、二次イオン化室をさしている。 Here, "primary particles" refers not only to primary ion particles such as rare gases in the case of SIMS, but also to
In the case of FAB, it also includes uncharged particles (those whose charge has been removed after being accelerated). Moreover, the "sample ionization chamber" usually refers to the secondary ionization chamber.
前記クロマトグラフ・シートは通常、該混合物
試料の各成分の展開方向に沿つて変位させられ、
該一次粒子の一定の流れが、順次各成分の二次イ
オン粒子を発生させることとなるように構成され
ている。 the chromatographic sheet is typically displaced along the direction of development of each component of the mixture sample;
The constant flow of primary particles is configured to sequentially generate secondary ion particles of each component.
前記クロマトグラフ・シートに対しては普通、
該一次粒子との衝突直前にマトリツクス剤を供給
するものとする。 For the chromatographic sheet, usually
The matrix agent is supplied immediately before the collision with the primary particles.
本発明の他の側面によれば、試料イオン化部に
隣接し、これと連通可能な試料導入室の末端開口
に、気密且つ非回転的に嵌合し、外部操作によつ
て該開口に対し抜き差し自在に変位するシヤフ
ト、および該シヤフト内側端部に絶縁物を介して
取り付けられ、該試料イオン化室内および試料導
入室内で、該シヤフトの変位に応じて直線変位し
うるブラケツトを含み、該ブラケツトは、導電性
クロマトグラフ・シートを導電状態で、一次粒子
ビームの照射下に保持し、且つ該変位中、二次イ
オン源部との接触導電を維持しうるものであるこ
とを特徴とする二次イオン質量分析計用試料走査
装置が提供される。 According to another aspect of the present invention, the sample introduction chamber is fitted airtightly and non-rotatably into the end opening of the sample introduction chamber adjacent to and in communication with the sample ionization section, and is inserted into and removed from the opening by external operation. A freely displaceable shaft, and a bracket attached to an inner end of the shaft via an insulator and capable of linearly displacing in accordance with the displacement of the shaft within the sample ionization chamber and the sample introduction chamber, the bracket comprising: A secondary ion, characterized in that it is capable of holding a conductive chromatographic sheet in a conductive state under irradiation with a primary particle beam, and maintaining contact conduction with a secondary ion source part during said displacement. A sample scanning device for a mass spectrometer is provided.
ここで、前記シヤフトには、その回転を防止す
るための並行支持棒が取り付けられており、該試
料導入室の末端部には、該並行支持棒を抜き差し
自在に嵌合保持する案内部材が設けられているこ
とが普通である。 Here, a parallel support rod is attached to the shaft to prevent its rotation, and a guide member is provided at the end of the sample introduction chamber to fit and hold the parallel support rod so that it can be freely inserted and removed. It is normal that
また、本発明装置においては、前記抜き差し自
在に変位するシヤフトおよびブラケツトに対応し
て、直線的に変位し得る前記導電性クロマトグラ
フ・シート薄層上の試料に対して、前記一次粒子
ビームとの衝突直前にマトリツクス剤を供給する
必要があり、このため当該装置の試料導入室内
に、例えばインクジエツト・プリンタなどで汎用
されている通常の圧電型ジエツトポンプを利用し
た前記マトリツクス剤の自動供給装置を設備して
おくことが好ましい。 In addition, in the apparatus of the present invention, the sample on the conductive chromatography sheet thin layer, which can be linearly displaced, corresponds to the shaft and bracket that can be freely inserted and removed, and the primary particle beam and the sample can be moved linearly. It is necessary to supply the matrix agent immediately before the collision, and for this reason, an automatic matrix agent supply device using a normal piezoelectric jet pump commonly used in inkjet printers, etc. is installed in the sample introduction chamber of the device. It is preferable to keep it.
なお、前記マトリツクス剤は試料のイオン化に
役立つ低蒸気圧有機化合物であり、望ましくは、
グリセリン、チオグリセリンおよびエタノールア
ミンよりなる群より選ばれたものである。 Note that the matrix agent is a low vapor pressure organic compound that helps in ionizing the sample, and preferably,
It is selected from the group consisting of glycerin, thioglycerin and ethanolamine.
前記したように本発明によれば、通常のLCま
たはGC操作によつては分解し、測定が困難ある
いは不能な混合物試料を薄層クロマトグラフイ
（TLC）で各成分スポツトの列として分離して得
た試料を導電性クロマトグラフ・シートからなる
試料保持体として、質量分析計の試料イオン化室
内で、該スポツトの列に沿つて変位させるもので
あり、かつ、この変位中前記記導電性クロマトグ
ラフ・シートが常時導電状態にあるように二次イ
オン源部との接触導電を維持するものであるの
で、この試料に対し、SIMSの場合、一次イオン
を、またFABの場合は非荷電高速粒子を衝突さ
せることにより、二次イオンすなわち試料の分子
イオンおよび分子のフラグメントイオンを各成分
ごと時系列に沿つて得ることが出来る。
As described above, according to the present invention, a mixture sample that is difficult or impossible to measure due to decomposition by normal LC or GC operations is separated as a row of individual component spots using thin layer chromatography (TLC). The obtained sample is used as a sample holder made of a conductive chromatograph sheet, and is displaced along the row of spots in the sample ionization chamber of a mass spectrometer, and during this displacement, the conductive chromatograph・Since the sheet maintains contact conductivity with the secondary ion source so that it is always in a conductive state, this sample is subjected to primary ions in the case of SIMS, and uncharged high-speed particles in the case of FAB. By colliding, secondary ions, that is, molecular ions and molecular fragment ions of the sample can be obtained for each component in time series.
以下、本発明を、添付の図面に示した実施例を
参照しながら詳細に説明する。
The invention will now be described in detail with reference to embodiments illustrated in the accompanying drawings.
第１図ａは、一般的な質量分析計の概略系統図
で、１０は試料イオン化部、６０は分析部、また
７０は検出部を示す。同図ｂは、SIMSを例にと
つた試料イオン化部１０の概略で、ａの面ｂ−ｂ
に沿う断面図である。 FIG. 1a is a schematic system diagram of a general mass spectrometer, in which 10 indicates a sample ionization section, 60 an analysis section, and 70 a detection section. Figure b is a schematic diagram of the sample ionization unit 10 using SIMS as an example, and the plane b-b of a
FIG.
一次イオン発生部１２（一次イオン源、レン
ズ、ガス衝突室、偏向電極などを含む）で作られ
たアルゴン、キセノン等の一次イオン粒子は矢印
２０に沿うビームとなつて、試料イオン化室（二
次イオン化室）１４に送られ試料保持体２２と衝
突して試料の二次イオンを発生させる。 Primary ion particles such as argon and xenon generated in the primary ion generation section 12 (including the primary ion source, lens, gas collision chamber, deflection electrode, etc.) become a beam along the arrow 20, and are transferred to the sample ionization chamber (secondary The sample is sent to the ionization chamber 14 and collides with the sample holder 22 to generate secondary ions of the sample.
一次イオン粒子は、試料イオン化室１４のスリ
ツト２８によつて絞られ細いビームとなつて、試
料を保持し、かつ二次イオン加速電圧と等しい電
位が保たれている試料保持体２２の表面に、その
法線に対し約70゜の角度をもつて入射し、試料と
衝突し、ほぼ法線に等しい出射角の二次イオン粒
子を発生させる。該粒子は、レンズ１６、イオン
源スリツト１８を通過し、矢印３０に沿うビーム
として分析部６０、次いで検出部７０に導かれ
る。２６は、粒子加速を補助するリペラーである
が、SIMSには必須でないので第２図では省略し
てある。 The primary ion particles are focused by the slit 28 of the sample ionization chamber 14 and become a narrow beam, which is applied to the surface of the sample holder 22 that holds the sample and is maintained at a potential equal to the secondary ion accelerating voltage. It enters at an angle of approximately 70° to the normal, collides with the sample, and generates secondary ion particles with an exit angle approximately equal to the normal. The particles pass through the lens 16, the ion source slit 18, and are guided as a beam along the arrow 30 to an analysis section 60 and then to a detection section 70. Reference numeral 26 is a repeller that assists particle acceleration, but it is omitted in FIG. 2 because it is not essential for SIMS.
ここに試料保持体として本発明においては、導
電性クロマトグラフ・シートを用いているので、
該シートを混合物試料の展開方向に沿つて変位さ
せ、該試料に一次イオン粒子を衝突させれば、含
有各成分の走査に対応して当該試料の二次イオン
が順次発生する。 Here, in the present invention, a conductive chromatography sheet is used as a sample holder, so
By displacing the sheet along the direction in which the mixture sample is developed and causing primary ion particles to collide with the sample, secondary ions of the sample are sequentially generated in accordance with the scanning of each component contained therein.
第２図は、本発明試料走査装置の概略図で、第
１図の面２−２に沿う断面に相当する。ここで、
試料イオン化部１０には、試料導入室３２が隣接
して設けられており、両者間は、任意に遮断、連
通が計りうるように、また両者の減圧状態は、そ
れぞれ個別に制御し得るものとなつている。すな
わち、測定準備の段階で、Ｏリング３６つきの扉
３４を閉じて両室間を遮断して、導入室３２を大
気圧に戻す。この状態で導入室３２を開き（片開
きが普通）、試料保持体２２をブラケツト２４に
装着して導入室３２を復元し、次いで導入室の減
圧を開始し、充分減圧された状態で、扉３４を開
き、両室間の連通を計る（第２図ｂでは扉３４の
図示を省略した）。 FIG. 2 is a schematic diagram of the sample scanning device of the present invention, and corresponds to a cross section taken along plane 2-2 of FIG. here,
A sample introduction chamber 32 is provided adjacent to the sample ionization section 10, and communication between the two can be arbitrarily interrupted and communicated, and the reduced pressure state of both can be controlled individually. It's summery. That is, at the measurement preparation stage, the door 34 with the O-ring 36 is closed to isolate the two chambers, and the introduction chamber 32 is returned to atmospheric pressure. In this state, the introduction chamber 32 is opened (one side is normally opened), the sample holder 22 is attached to the bracket 24, the introduction chamber 32 is restored, and then the pressure in the introduction chamber is started, and when the pressure is sufficiently reduced, the door is closed. 34 is opened to establish communication between the two chambers (the door 34 is not shown in FIG. 2b).
ブラケツト２４は、導入室３２の末端開口４０
に、Ｏリング４２によつて気密に嵌合しているシ
ヤフト４４の内側端部に絶縁碍子４６を介して取
り付けられている。該シヤフト４４には、並行支
持棒４８が取り付けられており、一方、該末端開
口４０には、並行支持棒４８を抜き差し自在に嵌
合保持する案内部材５０が設けられている。それ
ゆえ、該シヤフト４４は、その直線変位にさいし
回転しないようになつている。 Bracket 24 connects distal opening 40 of introduction chamber 32.
It is attached via an insulator 46 to the inner end of the shaft 44, which is airtightly fitted with an O-ring 42. A parallel support rod 48 is attached to the shaft 44, and a guide member 50 is provided in the end opening 40 to fit and hold the parallel support rod 48 so that it can be freely inserted and removed. The shaft 44 therefore does not rotate during its linear displacement.
イオン化部１０と導入室３２との連通および両
室の高真空が保たれた状態で、シヤフト４４を、
図面上左方に、任意の外部手段で変位させると、
試料保持体２２がイオン化部１０のイオン化室１
４に到達する（第２図ｂ）。この状態で、シヤフ
ト４４を、より慎重にかつ一定速度で変位させる
ことにより試料の走査が行なわれる。この変位手
段として、シヤフト４４または並行支持棒４８の
一方に、リニア・モータを取り付けてもよく、ま
た、たとえば、ラツク・ピニオン式またはナツ
ト・スクリユー式の微動装置（図示せず）を介し
てステツプ・モータを装着してもよい。 With the communication between the ionization section 10 and the introduction chamber 32 and the high vacuum maintained in both chambers, the shaft 44 is
When displaced to the left in the drawing by any external means,
The sample holder 22 is in the ionization chamber 1 of the ionization section 10
4 (Figure 2b). In this state, the sample is scanned by displacing the shaft 44 more carefully and at a constant speed. As means for this displacement, a linear motor may be attached to one of the shafts 44 or the parallel support rods 48, and a step may be provided, for example via a rack-and-pinion or nut-screw fine movement device (not shown).・A motor may be installed.
第３図は、試料保持体２２と、その関連部分の
拡大図（そのうちｂは、ａをシヤフトを中心に
90゜回転させた図面）であつて、試料保持体２２
として吸着剤層２１と基板２３を有する導電性ク
ロマトグラフ・シートが用いられていること、お
よびブラケツト２４には、集電レール２５が取り
付けられていることが示されている。 FIG. 3 is an enlarged view of the sample holder 22 and its related parts (of which b shows a with the shaft at the center).
(a drawing rotated by 90 degrees), in which the sample holder 22
It is shown that a conductive chromatographic sheet having an adsorbent layer 21 and a substrate 23 is used as the substrate, and that a current collection rail 25 is attached to the bracket 24.
なお、イオン化室１４は、試料保持体２２およ
び関連部材の側方からの貫通を許容するよう構成
されており、導電スプリング５４は、イオン化室
１４内で、集電レール２５との接触を保つための
ものである。 The ionization chamber 14 is configured to allow the sample holder 22 and related members to penetrate from the side, and the conductive spring 54 is configured to maintain contact with the current collection rail 25 within the ionization chamber 14. belongs to.
また、イオン化室１４の前面にもうけられたス
リツト・デイスク５６には、前記ビーム・スリツ
ト２８が設けられている。また１６は、二次イオ
ン・ビーム３０を分析部に導くレンズである。 Further, the beam slit 28 is provided in a slit disk 56 provided on the front surface of the ionization chamber 14. Further, 16 is a lens that guides the secondary ion beam 30 to the analysis section.
一方、５９は、マトリツクス剤添加用ジエツ
ト・ポンプで、たとえば、インクジエツト・プリ
ンターで汎用されている圧電ヘツドを転用するこ
とが出来る。 On the other hand, 59 is a jet pump for adding matrix agent, and for example, a piezoelectric head commonly used in inkjet printers can be used.
測定例 １
３種のペプチドの混合物を対象試料として、通
常の上昇法展開を行なつた。TLCプレートとし
てメルク・アルミシート（Art.5583）を、展開溶
媒として酢酸エチル／酢酸／水：４／１／１を用
い第４図ａ中程にRf値を示すように分離するこ
とが出来た。Measurement Example 1 A mixture of three types of peptides was used as a target sample and the usual ascending method was developed. Using Merck aluminum sheet (Art.5583) as the TLC plate and ethyl acetate/acetic acid/water: 4/1/1 as the developing solvent, we were able to separate the Rf value as shown in the middle of Figure 4a. .
このシートの展開スポツトを有する部分を切断
して試料保持体２２とし、前記実施例装置のブラ
ケツト２４に装着した。本測定に用いた日立製Ｍ
−80シリーズ質量分析計の導入室３２は、本発明
の目的に沿うように実施例にしたがつて改造し
た。実施例中の操作にならいマトリツクス剤を施
した試料保持体２２につきSIMSを行なつた結
果、第４図ａに示すトータルイオンクロマトグラ
ムと同図（ｂ，ｃおよびｄ）に示す個別ペプチド
のマススペクトルを得た。 A portion of this sheet having the development spot was cut to form a sample holder 22, which was attached to the bracket 24 of the apparatus of the embodiment. Hitachi M used for this measurement
The introduction chamber 32 of the -80 series mass spectrometer was modified in accordance with the embodiments to meet the objectives of the present invention. As a result of performing SIMS on the sample holder 22 coated with a matrix agent following the procedure in Examples, the total ion chromatogram shown in Figure 4a and the mass of individual peptides shown in the same figure (b, c, and d) were obtained. Obtained the spectrum.
なお、ａは、ｍ／z200〜800のマススペクトル
範囲で、80回の繰り返し磁場掃引を行ない、トー
タルイオンの強度でクロマトグラムをデータ処理
装置で描いたものである。ここで横軸（下）は、
磁場掃引回数（Scan.No）、同（上）は、磁場掃
引開始からの時間（分）を示す。中程に描かれた
Rf値は、TLCの際の値である。（以後のトータル
イオンクロマトグラムについても同様）。 Note that a is a chromatogram drawn with a data processing device using the total ion intensity after performing repeated magnetic field sweeps 80 times in the mass spectrum range of m/z 200 to 800. Here, the horizontal axis (bottom) is
The number of magnetic field sweeps (Scan.No.) (above) indicates the time (minutes) from the start of the magnetic field sweep. drawn in the middle
The Rf value is the value at the time of TLC. (The same applies to the subsequent total ion chromatograms).
また、ｂのScan.No.15−10、ｃのScan.No.32−
27、およびｄのScan.No.45−42は、それぞれ掃引
番号15、32、45番目のスペクトルを表示し、減算
に用いた10、27、42は、それぞれ同様にその番号
のスペクトルをバツクグラウンドとして用いたこ
とを示している。なお、横軸は、質量数、縦軸
は、相対イオン強度をあらわす。 Also, Scan.No.15-10 for b, Scan.No.32- for c
Scan.No. 45-42 in 27 and d display the spectra with sweep numbers 15, 32, and 45, respectively, and 10, 27, and 42 used for subtraction similarly display the spectra with those numbers in the background. It shows that it was used as Note that the horizontal axis represents mass number, and the vertical axis represents relative ion intensity.
ｂ，ｃおよびｄに示された個別のペプチドは、
共に分子イオン領域に水素付加したMH+が、明
瞭に観測されている。その他特徴的な開裂イオン
も見られ、それぞれ分離した個別ペプチドの、通
常のSIMS法で測定したものと略同等のスペクト
ルである。 The individual peptides shown in b, c and d are
In both cases, MH + with hydrogen added to the molecular ion region is clearly observed. Other characteristic cleavage ions are also seen, and the spectrum is approximately equivalent to that measured by the normal SIMS method of each separated individual peptide.
なお、スペクトル中＊を付したもの（ｍ／
z185、277、369、461）は、使用したマトリツク
ス剤由来のイオンであり、それぞれ２、３、４お
よび５量体の水素付加イオンに相当する。 In addition, those marked with * in the spectrum (m/
z185, 277, 369, 461) are ions derived from the matrix agent used, and correspond to hydrogenated ions of 2, 3, 4, and 5 mer, respectively.
こうしたペプチド混合物は、GCで分離出来な
いのは勿論、LCで分離出来たとしてもイオン化
前に分解することが多く、これまで測定が困難で
あつた。 It goes without saying that such peptide mixtures cannot be separated by GC, and even if they can be separated by LC, they often decompose before ionization, making measurement difficult until now.
測定例 ２
別の３種ペプチド混合物試料について、測定例
１と同様の実験を行ない、第５図に示す分離状態
の良好なトータルイオンクロマトグラムを得た。
ここでは、TLC展開溶媒として、クロロホル
ム／メタノール：39／１を用いた。Measurement Example 2 The same experiment as in Measurement Example 1 was conducted on another three-type peptide mixture sample, and a total ion chromatogram with good separation shown in FIG. 5 was obtained.
Here, chloroform/methanol: 39/1 was used as the TLC developing solvent.
測定例 ３
水溶性ビタミン混合物試料についての、同様な
測定において得られた結果を第６図に示す。
TLC展開溶媒としては、アセトン／水：９／１
を用い良好な分離状態のトータルイオンクロマト
グラムを得た。Measurement Example 3 The results obtained in a similar measurement on a water-soluble vitamin mixture sample are shown in FIG.
TLC developing solvent: acetone/water: 9/1
A total ion chromatogram with good separation was obtained.
測定例 ４
イブプロフエンのメチルベンジルアミド誘導体
の光学異性体混合物試料をベンゼン／酢酸エチ
ル／メタノール混合溶媒でTLC展開し、これを
測定例１と同様に処理して、第７図に示す結果を
得た。Measurement Example 4 A sample of the optical isomer mixture of the methylbenzylamide derivative of ibuprofen was developed by TLC using a mixed solvent of benzene/ethyl acetate/methanol and treated in the same manner as in Measurement Example 1 to obtain the results shown in Figure 7. .
そのうちａは、トータルイオンクロマトグラム
であり、ｍ／z310＊10.0は、水素付加分子イオン
MH+のマスクロマトグラム、＊10.0は、10倍の
倍率を掛けたことを示す。また、ｂは、マススペ
クトルであり、上の構造式中の＊は、プロピル基
の根本の炭素が不整炭素であることを示してい
る。 Of these, a is the total ion chromatogram, and m/z310*10.0 is the hydrogenated molecular ion.
Mass chromatogram of MH + , *10.0 indicates multiplication by 10x magnification. Further, b is a mass spectrum, and * in the above structural formula indicates that the root carbon of the propyl group is an asymmetric carbon.
TLCプレート上で非常に接近した両者を互い
に混同することなく、良く分離して観測すること
が出来た。 It was possible to observe the two particles, which were very close together on the TLC plate, separated well without confusing them with each other.
このほか、シリル化あるいは過メチル化しなけ
ればGCで分離しがたい糖類を直接分離・測定す
ることが出来た。 In addition, we were able to directly separate and measure sugars that are difficult to separate by GC without silylation or permethylation.
上記したように本発明によれば、その吸着剤薄
層に各成分を表わすスポツトの列としてクロマト
グラフ展開された導電性クロマトグラフ・シート
を試料保持体とし、該試料保持体を導電状態のま
ま前記スポツトの列に沿つて変位させ得るもので
あるので、この変位中該試料に対して一次イオン
粒子または非荷電高速粒子を衝突させることによ
つて二次イオン、すなわち当該試料の分子イオン
および／または該分子のフラグメントイオンを各
成分ごとに順次効率よく、しかも高精度に得るこ
とができる。従つて、本発明によれば、これまで
分離機能と測定機能を併有する既製の質量分析
法、すなわち高価かつ複雑な装置を必要とする
GC／MSおよびLC／MSのいずれによつても、
分離・測定が困難であつた混合物試料の分析を、
在来のSIMS装置に簡単な付加装置を設けるだけ
で、容易に実施できるという大きな工業的効果が
ある。
As described above, according to the present invention, a conductive chromatographic sheet is used as a sample holder, and the conductive chromatographic sheet is chromatographically developed as a row of spots representing each component on the adsorbent thin layer, and the sample holder remains in a conductive state. Since the spot can be displaced along the row of spots, secondary ions, that is, molecular ions and/or molecules of the sample, are generated by colliding the sample with primary ion particles or uncharged high-speed particles during this displacement. Alternatively, fragment ions of the molecule can be obtained sequentially for each component efficiently and with high precision. Therefore, according to the present invention, hitherto an off-the-shelf mass spectrometry method that combines separation and measurement functions, i.e., requires expensive and complicated equipment.
By both GC/MS and LC/MS,
Analysis of mixture samples that were difficult to separate and measure.
It has a great industrial effect because it can be easily implemented by simply adding a simple additional device to a conventional SIMS device.
第１図ａは、一般的な質量分析計の概略系統
図、同ｂは、SIMSを例にとつた試料イオン化部
のａのｂ〜ｂに沿う断面に相当する概略図、第２
図は、本発明試料走査装置の一実施例の第１図ｂ
の２〜２に沿う断面に相当する概略図、第３図
は、第２図中の試料保持体及び関連部分の拡大
図、および第４〜７図は、種々の試料についての
測定例のトータルイオンクロマトグラムおよび／
またはマススペクトラムである。
１０……試料イオン化部、１２……一次イオン
発生部、１４……試料イオン化室、１６……レン
ズ、１８……イオン源スリツト、２０……一次イ
オンビーム、２１……吸着剤薄層、２２……試料
保持体、２３……基板、２４……ブラケツト、２
５……集電レール、２６……リペラー、２８……
ビーム・スリツト、３０……二次イオンビーム、
３２……試料導入室、３４……扉、３６……Ｏリ
ング、４０……末端部、４２……Ｏリング、４４
……シヤフト、４６……絶縁碍子、４８……並行
支持棒、５０……案内部材、５４……導電スプリ
ング、５６……スリツト・デイスク、５９……ジ
エツト・ポンプ。
Figure 1a is a schematic system diagram of a general mass spectrometer, Figure 1b is a schematic diagram corresponding to a cross section along b to b of a of a sample ionization section using SIMS as an example, and Figure 2.
The figure is FIG. 1b of an embodiment of the sample scanning device of the present invention.
3 is an enlarged view of the sample holder and related parts in FIG. 2, and FIGS. 4 to 7 are totals of measurement examples for various samples. Ion chromatogram and/or
Or mass spectrum. DESCRIPTION OF SYMBOLS 10... Sample ionization part, 12... Primary ion generation part, 14... Sample ionization chamber, 16... Lens, 18... Ion source slit, 20... Primary ion beam, 21... Adsorbent thin layer, 22 ... Sample holder, 23 ... Substrate, 24 ... Bracket, 2
5... Current collection rail, 26... Repeller, 28...
Beam slit, 30...Secondary ion beam,
32...Sample introduction chamber, 34...Door, 36...O ring, 40...End part, 42...O ring, 44
... Shaft, 46 ... Insulator, 48 ... Parallel support rod, 50 ... Guide member, 54 ... Conductive spring, 56 ... Slit disk, 59 ... Jet pump.
Claims (1)
変位可能に配置された導電性クロマトグラフ・シ
ート表面の吸着剤薄層に各成分を表わすスポツト
の列としてクロマトグラフ展開された混合物試料
に対し、その各スポツトに順次衝突する一次粒子
の連続的な流れを形成すること、および該一次粒
子との衝突によつて発生した該試料の各成分を表
わす二次イオン粒子を順次、質量分析計の分析部
に送り込むことを特徴とする試料走査形質量分析
方法。 ２ 該クロマトグラフ・シートを、該混合物試料
の各成分の展開方向に沿つて変位させ、該一次粒
子の一定の流れが、順次各成分の二次イオン粒子
を発生させることとなるように構成したことを特
徴とする特許請求の範囲第１項に記載の方法。 ３ 該クロマトグラフ・シートに対し、該一次イ
オンとの衝突直前にマトリツクス剤を供給するも
のであることを特徴とする特許請求の範囲第１項
に記載の方法。 ４ 該マトリツクス剤が、試料のイオン化に役立
つ低蒸気圧有機化合物であることを特徴とする特
許請求の範囲第３項に記載の方法。 ５ 該低蒸気圧有機化合物が、グリセリン、チオ
グリセリンおよびエタノールアミンよりなる群よ
り選ばれたものであることを特徴とする特許請求
の範囲第４項に記載の方法。 ６ 試料イオン化部に隣接し、これと連通可能な
試料導入室の末端開口に、気密且つ非回転的に嵌
合し、外部操作によつて該開口に対し抜き差し自
在に変位するシヤフト、および該シヤフト内側端
部に絶縁物を介して取り付けられ、該試料イオン
化部内および試料導入室内で、該シヤフトの変位
に応じて直線変位しうるブラケツトを含み、該ブ
ラケツトは、導電性クロマトグラフ・シートを導
電状態で、一次粒子ビームの照射下に保持し、且
つ該変位中、二次イオン源部との接触導電を維持
しうるものであることを特徴とする試料走査形質
量分析計用試料走査装置。 ７ 該シヤフトに、その回転を防止するための並
行支持棒が取り付けられており、該試料導入室の
末端部に、該並行支持棒を抜き差し自在に嵌合保
持する案内部材が設けられている特許請求の範囲
第６項に記載の装置。 ８ 該試料導入室内に、マトリツクス剤供給装置
が設けられており、該変位に応じて該クロマトグ
ラフ・シート薄層上の試料に対してマトリツクス
剤が、該一次粒子ビームとの衝突直前に供給され
るようにされた特許請求の範囲第６項に記載の装
置。 ９ 該マトリツクス剤が試料のイオン化に役立つ
低蒸気圧有機化合物である特許請求の範囲第８項
に記載の装置。 １０ 該低蒸気圧有機化合物が、グリセリン、チ
オグリセリンおよびエタノールアミンよりなる群
より選ばれたものである特許請求の範囲第８項に
記載の装置。 １１ 該マトリツクス剤供給装置が、圧電型ジエ
ツト・ポンプである特許請求の範囲第６項に記載
の装置。[Scope of Claims] 1. A mixture sample chromatographically developed as a row of spots representing each component on a thin layer of adsorbent on the surface of a conductive chromatograph sheet arranged so as to be linearly displaceable in a sample ionization chamber of a mass spectrometer. Then, a continuous flow of primary particles is formed that collides with each spot in sequence, and secondary ion particles representing each component of the sample generated by the collision with the primary particles are sequentially subjected to mass spectrometry analysis. A sample scanning mass spectrometry method characterized by sending the sample to the analysis section of the analyzer. 2. The chromatographic sheet is displaced along the direction of development of each component of the mixture sample, and the constant flow of the primary particles is configured to sequentially generate secondary ion particles of each component. A method according to claim 1, characterized in that: 3. The method according to claim 1, wherein a matrix agent is supplied to the chromatographic sheet immediately before the collision with the primary ions. 4. A method according to claim 3, characterized in that the matrix agent is a low vapor pressure organic compound that aids in the ionization of the sample. 5. The method of claim 4, wherein the low vapor pressure organic compound is selected from the group consisting of glycerin, thioglycerin and ethanolamine. 6. A shaft that fits airtightly and non-rotationally into the end opening of the sample introduction chamber that is adjacent to and communicates with the sample ionization section, and that can be freely inserted into and removed from the opening by an external operation, and the shaft. The bracket includes a bracket that is attached to the inner end via an insulator and can be linearly displaced within the sample ionization section and the sample introduction chamber according to the displacement of the shaft, and the bracket keeps the conductive chromatography sheet in a conductive state. A sample scanning device for a sample scanning mass spectrometer, characterized in that it can be held under irradiation with a primary particle beam and maintain contact conductivity with a secondary ion source during the displacement. 7 A patent in which a parallel support rod is attached to the shaft to prevent its rotation, and a guide member is provided at the end of the sample introduction chamber to fit and hold the parallel support rod so that it can be freely inserted and removed. Apparatus according to claim 6. 8 A matrix agent supply device is provided in the sample introduction chamber, and a matrix agent is supplied to the sample on the thin layer of the chromatographic sheet according to the displacement immediately before the collision with the primary particle beam. 7. A device according to claim 6, wherein the device is adapted to: 9. The apparatus of claim 8, wherein the matrix agent is a low vapor pressure organic compound that aids in ionizing the sample. 10. The device of claim 8, wherein the low vapor pressure organic compound is selected from the group consisting of glycerin, thioglycerin, and ethanolamine. 11. The device according to claim 6, wherein the matrix agent supply device is a piezoelectric jet pump.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60104883A JPS61260149A (en) | 1985-05-15 | 1985-05-15 | Specimen scan type mass spectrometry and specimen scanner |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60104883A JPS61260149A (en) | 1985-05-15 | 1985-05-15 | Specimen scan type mass spectrometry and specimen scanner |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61260149A JPS61260149A (en) | 1986-11-18 |
| JPH0437542B2 true JPH0437542B2 (en) | 1992-06-19 |
Family
ID=14392579
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60104883A Granted JPS61260149A (en) | 1985-05-15 | 1985-05-15 | Specimen scan type mass spectrometry and specimen scanner |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61260149A (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11139155B2 (en) | 2017-11-28 | 2021-10-05 | Hamamatsu Photonics K.K. | Laser desorption/ionization method and mass spectrometry method |
| US11335546B2 (en) | 2017-11-28 | 2022-05-17 | Hamamatsu Photonics K.K. | Laser desorption/ionization method, mass spectrometry method, sample support body, and manufacturing method of sample support body |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5032076B2 (en) * | 2006-09-12 | 2012-09-26 | 株式会社テクノフロント | Mass spectrometer |
| JP5947533B2 (en) * | 2011-01-19 | 2016-07-06 | キヤノン株式会社 | Information acquisition method |
-
1985
- 1985-05-15 JP JP60104883A patent/JPS61260149A/en active Granted
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11139155B2 (en) | 2017-11-28 | 2021-10-05 | Hamamatsu Photonics K.K. | Laser desorption/ionization method and mass spectrometry method |
| US11335546B2 (en) | 2017-11-28 | 2022-05-17 | Hamamatsu Photonics K.K. | Laser desorption/ionization method, mass spectrometry method, sample support body, and manufacturing method of sample support body |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61260149A (en) | 1986-11-18 |
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